Genetic variants of alcohol‐metabolizing enzymes in Brugada syndrome: Insights into syncope after drinking alcohol
Genetic variants of alcohol‐metabolizing enzymes in Brugada syndrome: Insights into syncope after drinking alcohol
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布鲁格达综合征酒精代谢酶的遗传变异：饮酒后晕厥的见解
DOI：
10.1002/joa3.12227
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发表时间：
2019
影响因子：
2
通讯作者：
Horie Minoru
中科院分区：
文献类型：
--
作者：
Wu Qi;Hayashi Hideki;Hira Daiki;Sonoda Keiko;Ueshima Satoshi;Ohno Seiko;Makiyama Takeru;Terada Tomohiro;Katsura Toshiya;Miura Katsuyuki;Horie Minoru
背景已知布鲁格达综合征（BrS）患者饮酒后会出现心律失常事件，建议避免过量饮酒。然而，酒精引起的心脏事件的机制尚不清楚。本研究旨在检验酒精代谢酶的活性是否决定饮酒后致命性心律失常事件的假设。方法共有 198 名日本 BrS 患者参与本研究。这些患者被分为有症状组 (n = 90) 和无症状组 (n = 108)。前者被分为酒精相关组（饮酒后晕厥，n = 16）和酒精无关组（n = 74）。采用聚合酶链式反应测定编码乙醇脱氢酶1B（ADH1B）和乙醛脱氢酶2（ALDH2）的基因的遗传变异。结果ALDH2的基因型分布在有症状组和无症状组之间以及酒精相关组和非酒精相关组之间没有显着差异。 ADH1B 的基因型分布在有症状组和无症状组之间没有显着差异，但 ADH1BHis/His 基因型在酒精相关组中显着高于酒精无关组（81.3% vs 50%，P=0.023）。在多变量逻辑回归分析中，ADH1BHis/His 的基因型与饮酒后晕厥独立相关（比值比，5.746；95% 置信区间，1.580‐28.421；P= .007）。 结论 在我们的 BrS 队列中，饮酒后心律失常事件与酒精代谢酶 ADH1B 活性增强相关。因此，改变生活方式以避免过量饮酒值得关注。
BackgroundPatients with Brugada syndrome (BrS) are known to have arrhythmic events after alcohol drinking and are recommended to avoid its excessive intake. Mechanisms underlying the alcohol‐induced cardiac events are however unknown. This study aimed to test the hypothesis whether activity of alcohol‐metabolizing enzymes determines fatal arrhythmic events after drinking alcohol.MethodsA total of 198 Japanese patients with BrS were enrolled in this study. These patients were classified into symptomatic (n = 90) and asymptomatic (n = 108) groups. The former was divided into an alcohol‐related group (syncope after alcohol drinking, n = 16) and an alcohol‐unrelated group (n = 74). Polymerase chain reaction was performed to determine genetic variants of genes encoding alcohol dehydrogenase 1B (ADH1B) and aldehyde dehydrogenase 2 (ALDH2).ResultsThe genotype distribution forALDH2was not significantly different between symptomatic and asymptomatic groups and between alcohol‐related and alcohol‐unrelated groups. The genotype distribution forADH1Bwas not significantly different between symptomatic and asymptomatic groups, but the genotypeADH1BHis/His was significantly more prevalent in the alcohol‐related group than in the alcohol‐unrelated group (81.3% vs 50%,P= .023). In multivariate logistic regression analysis, the genotype ofADH1BHis/His was independently associated with syncope after alcohol drinking (odds ratio, 5.746; 95% confidence interval, 1.580‐28.421;P= .007).ConclusionsArrhythmic events after alcohol drinking was associated with enhanced activity of alcohol‐metabolizing enzymeADH1Bin our cohort of BrS. Therefore, the lifestyle change to avoid the excessive alcohol intake deserves attention.